Ulcerative Colitis MedDRA version: 19.0 Level: SOC Classification code 10017947 Term: Gastrointestinal disorders System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Trade Name: Mercaptopurine (Puri-Nethol)
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Academic Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Confirmed diagnosis of UC by endoscopy and histopathology 2. Patients between 18 and 80 years of age 3. Active disease, despite oral treatment with at least 2g/day 5-ASA 4. Treatment with oral corticosteroids is required Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Prior treatment with thiopurines 2. Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab) 3. Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician.) 4. Chronic Obstructive Pulmonary Disease (COPD) 5. Acute coronary heart disease 6. (Bacterial) gastroenteritis has to be treated first 7. Coagulation disorders 8. Active malignancy 9. History of colonic dysplasia/cancer 10. Extensive colonic resection, i.e. subtotal colectomy with less than 15 cm colon in situ 11. Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics. 12. Known systemic fungal infections or parasitic infections have to be treated first 13. Known duodenal or ventricular ulcus 14. Substance abuse, such as alcohol (at least 80 gram/day – one standard glass contains 10 gram of alcohol), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded 15. Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician) 16. Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening. 17. Leucopenia (Neutrophil count below 1,8x10^9/L) 18. Thrombopenia (Platelets below 90x10^9/L) 19. Elevated liver enzymes (over 2x ULN) 20. Abnormal renal function (eGFR below 30 mL/min) 21. Other conditions which in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the proposed this study is to evaluate the efficacy of optimized thiopurine therapy. Therapeutic drug monitoring (TDM) will be applied in order to optimize treatment outcomes and objective endoscopic endpoints will be used. Optimized use of thiopurines may lead to prolonged and better disease outcome and avoidance of costly biological therapy or surgery. ;Secondary Objective: Secondary objectives are to conduct a cost-utility and budget impact analysis of optimized thiopurine therapy and to identify biomarkers as potential predictors of thiopurine response in mucosal biopsies, feces and blood.;Primary end point(s): The main endpoint of this study is clinical and endoscopic remission, which we defined as a SCCAI-score of maximum 4, a UCEIS-score of maximum 3 and a total Mayo-score of maximum 2, with no individual subscore above 1.;Timepoint(s) of evaluation of this end point: One year after start of the treatment (week 52) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Occurrence of (serious) adverse events ((S)AE) - Leukocyte counts - Liver function tests - Occurrence of subjective thiopurine intolerance - 6-TGN levels - 6-MMP levels - Occurrence of treatment failure - Occurrence of flares and upscaling treatment / escape medication - Treatment costs - Quality of life - Biomarkers, cell types and microbiome in colon biopsies - Fecal Volatile Organic Compounds (VOC's) - Fecal microbiome sequencing - RAC genotypes in blood samples ;Timepoint(s) of evaluation of this end point: Different time-points during one year of treatment. | — |
Countries
Netherlands
Contacts
Public ContactMark Löwenberg
Academic Medical Centre
Outcome results
None listed